Bottom Line:
Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction.The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated.These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

Affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an , China.

ABSTRACTOsteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer's disease (AD) than the age-matched non-dementia individuals. Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In this study, feeding a high-fat diet (HFD, 45% calorie from fat) to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning, and memory performance of the transgenic mice measured by T maze and Morris water maze, compared with the mice fed a normal-fat diet (10% calorie from fat). In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

Figure 1: High-fat-diet-induced weight gain in APP/PS1 mice. Throughout the experiment, the body weights of C57BL/6 and APP/PS1 mice had no difference, and significant body weight gain was induced after HFD feeding for 8 weeks (at 22 weeks) and sustained growing from then on (A). The ratio of parametric fat pad weight to body weight (B) of APP/PS1 + HFD mice was significantly higher than that of the C57BL/6 and APP/PS1 mice. The serum level of total cholesterol in APP/PS1 + HFD mice was higher than those in the other two mice groups (C). No difference in serum triglycerides was found among the three groups (D). Data were means ± SEM. n = 10 for C57BL/6 mice, n = 12 for APP/PS1 mice, and n = 11 for APP/PS1 + HFD mice for body weight. n = 7 for C57BL/6 mice, n = 9 for APP/PS1 mice, and n = 8 for APP/PS1 + HFD mice for other measurements. All results were analyzed by one-way ANOVA, followed by Newman–Keuls post hoc test, except that the body weight result was analyzed by two-way ANOVA, followed by Bonferroni’s post hoc test. ***p < 0.001.

Mentions:
During the feeding period, the initial body weights of the mice were 21.66 ± 1.29 g, and the final body weights of APP/PS1 + HFD mice (46.00 ± 9.72 g) were approximately 77.2 and 68.8% greater than those of C57BL/6 (25.96 ± 1.29 g) and APP/PS1 mice (27.25 ± 1.45 g), respectively, whereas no difference was found between the body weights of the C57BL/6 mice and APP/PS1 groups (Figure 1A). The ratio of the perimetric fat pad weight to body weight was 1.7 and 1.0 times higher in the APP/PS1 + HFD mice than those of the C57BL/6 and APP/PS1 mice, respectively (Figure 1B). A higher level of serum cholesterol was observed in the transgenic mice that were fed the HFD, while levels of serum triglycerides were not different among all groups (Figures 1C,D).

Figure 1: High-fat-diet-induced weight gain in APP/PS1 mice. Throughout the experiment, the body weights of C57BL/6 and APP/PS1 mice had no difference, and significant body weight gain was induced after HFD feeding for 8 weeks (at 22 weeks) and sustained growing from then on (A). The ratio of parametric fat pad weight to body weight (B) of APP/PS1 + HFD mice was significantly higher than that of the C57BL/6 and APP/PS1 mice. The serum level of total cholesterol in APP/PS1 + HFD mice was higher than those in the other two mice groups (C). No difference in serum triglycerides was found among the three groups (D). Data were means ± SEM. n = 10 for C57BL/6 mice, n = 12 for APP/PS1 mice, and n = 11 for APP/PS1 + HFD mice for body weight. n = 7 for C57BL/6 mice, n = 9 for APP/PS1 mice, and n = 8 for APP/PS1 + HFD mice for other measurements. All results were analyzed by one-way ANOVA, followed by Newman–Keuls post hoc test, except that the body weight result was analyzed by two-way ANOVA, followed by Bonferroni’s post hoc test. ***p < 0.001.

Mentions:
During the feeding period, the initial body weights of the mice were 21.66 ± 1.29 g, and the final body weights of APP/PS1 + HFD mice (46.00 ± 9.72 g) were approximately 77.2 and 68.8% greater than those of C57BL/6 (25.96 ± 1.29 g) and APP/PS1 mice (27.25 ± 1.45 g), respectively, whereas no difference was found between the body weights of the C57BL/6 mice and APP/PS1 groups (Figure 1A). The ratio of the perimetric fat pad weight to body weight was 1.7 and 1.0 times higher in the APP/PS1 + HFD mice than those of the C57BL/6 and APP/PS1 mice, respectively (Figure 1B). A higher level of serum cholesterol was observed in the transgenic mice that were fed the HFD, while levels of serum triglycerides were not different among all groups (Figures 1C,D).

Bottom Line:
Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction.The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated.These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.

Affiliation:
Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University , Xi'an , China.

ABSTRACTOsteoporosis is negatively correlated with body mass, whereas both osteoporosis and weight loss occur at higher incidence during the progression of Alzheimer's disease (AD) than the age-matched non-dementia individuals. Given that there is no evidence that being overweight is associated with AD-type cognitive dysfunction, we hypothesized that moderate weight gain might have a protective effect on the bone loss in AD without exacerbating cognitive dysfunction. In this study, feeding a high-fat diet (HFD, 45% calorie from fat) to female APP/PS1 transgenic mice, an AD animal model, induced weight gain. The bone mineral density, microarchitecture, and biomechanical properties of the femurs were then evaluated. The results showed that the middle-aged female APP/PS1 transgenic mice were susceptible to osteoporosis of the femoral bones and that weight gain significantly enhanced bone mass and mechanical properties. Notably, HFD was not detrimental to brain insulin signaling and AβPP processing, as well as to exploration ability and working, learning, and memory performance of the transgenic mice measured by T maze and Morris water maze, compared with the mice fed a normal-fat diet (10% calorie from fat). In addition, the circulating levels of leptin but not estradiol were remarkably elevated in HFD-treated mice. These results suggest that a body weight gain induced by the HFD feeding regimen significantly improved bone mass in female APP/PS1 mice with no detriments to exploration ability and spatial memory, most likely via the action of elevated circulating leptin.